6-31536810-G-T

Variant names:

• chr6-31536810-G-T
• rs3130057
• NM_004640.7:c.433-127C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004640.7(DDX39B):​c.433-127C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.829 in 1,187,230 control chromosomes in the GnomAD database, including 409,761 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.85 (54769 hom., cov: 32)
  • Exomes 𝑓: 0.83 (354992 hom.)
• Consequence: DDX39B NM_004640.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.17
• Publications: 15 publications found

Genes affected

DDX39B (HGNC:13917): (DExD-box helicase 39B) This gene encodes a member of the DEAD box family of RNA-dependent ATPases that mediate ATP hydrolysis during pre-mRNA splicing. The encoded protein is an essential splicing factor required for association of U2 small nuclear ribonucleoprotein with pre-mRNA, and it also plays an important role in mRNA export from the nucleus to the cytoplasm. This gene belongs to a cluster of genes localized in the vicinity of the genes encoding tumor necrosis factor alpha and tumor necrosis factor beta. These genes are all within the human major histocompatibility complex class III region. Mutations in this gene may be associated with rheumatoid arthritis. Alternative splicing results in multiple transcript variants. Related pseudogenes have been identified on both chromosomes 6 and 11. Read-through transcription also occurs between this gene and the upstream ATP6V1G2 (ATPase, H+ transporting, lysosomal 13kDa, V1 subunit G2) gene. [provided by RefSeq, Feb 2011]

ATP6V1G2-DDX39B (HGNC:41999): (ATP6V1G2-DDX39B readthrough (NMD candidate)) This locus represents naturally occurring read-through transcription between the neighboring ATP6V1G2 (ATPase, H+ transporting, lysosomal 13kDa, V1 subunit G2) and DDX39B (DEAD box polypeptide 39B) genes located in the major histocompatibility complex class III region of chromosome 6. The read-through transcript and is a candidate for nonsense-mediated mRNA decay (NMD), and is thus unlikely to produce a protein product. [provided by RefSeq, Feb 2011]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.904 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DDX39B	NM_004640.7	c.433-127C>A		intron_variant	Intron 4 of 10	ENST00000396172.6	NP_004631.1
DDX39B	NM_080598.6	c.433-127C>A		intron_variant	Intron 4 of 10		NP_542165.1
DDX39B	NR_037852.2	n.398-127C>A		intron_variant	Intron 2 of 8
ATP6V1G2-DDX39B	NR_037853.1	n.1236-127C>A		intron_variant	Intron 6 of 12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DDX39B	ENST00000396172.6	c.433-127C>A		intron_variant	Intron 4 of 10	1	NM_004640.7	ENSP00000379475.1
ATP6V1G2-DDX39B	ENST00000376185.5	n.*647-127C>A		intron_variant	Intron 6 of 12	2		ENSP00000365356.1

Frequencies

GnomAD3 genomes AF: 0.847 AC: 128877 AN: 152070 Hom.: 54712 Cov.: 32

Gnomad AFR AF: 0.876

Gnomad AMI AF: 0.827

Gnomad AMR AF: 0.868

Gnomad ASJ AF: 0.940

Gnomad EAS AF: 0.926

Gnomad SAS AF: 0.923

Gnomad FIN AF: 0.824

Gnomad MID AF: 0.908

Gnomad NFE AF: 0.813

Gnomad OTH AF: 0.860

GnomAD4 exome AF: 0.826 AC: 854883 AN: 1035042 Hom.: 354992 AF XY: 0.830 AC XY: 424637 AN XY: 511850

African (AFR) AF: 0.887 AC: 20675 AN: 23314

American (AMR) AF: 0.873 AC: 17094 AN: 19582

Ashkenazi Jewish (ASJ) AF: 0.938 AC: 16394 AN: 17470

East Asian (EAS) AF: 0.921 AC: 31551 AN: 34274

South Asian (SAS) AF: 0.926 AC: 53517 AN: 57776

European-Finnish (FIN) AF: 0.820 AC: 25715 AN: 31376

Middle Eastern (MID) AF: 0.912 AC: 4294 AN: 4710

European-Non Finnish (NFE) AF: 0.808 AC: 647559 AN: 800948

Other (OTH) AF: 0.835 AC: 38084 AN: 45592

GnomAD4 genome AF: 0.848 AC: 128992 AN: 152188 Hom.: 54769 Cov.: 32 AF XY: 0.852 AC XY: 63377 AN XY: 74404

African (AFR) AF: 0.876 AC: 36388 AN: 41518

American (AMR) AF: 0.868 AC: 13271 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.940 AC: 3262 AN: 3470

East Asian (EAS) AF: 0.926 AC: 4802 AN: 5186

South Asian (SAS) AF: 0.923 AC: 4456 AN: 4828

European-Finnish (FIN) AF: 0.824 AC: 8714 AN: 10572

Middle Eastern (MID) AF: 0.905 AC: 266 AN: 294

European-Non Finnish (NFE) AF: 0.813 AC: 55259 AN: 68004

Other (OTH) AF: 0.861 AC: 1820 AN: 2114

Alfa AF: 0.835 Hom.: 53036

Bravo AF: 0.851

Asia WGS AF: 0.866 AC: 3012 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.15
DANN	Benign	0.52
PhyloP100		-1.2
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs3130057; hg19: chr6-31504587;